Vil 32 no. 1, 2008.pmd

BANGLADESH J CHILD HEALTH 2008; VOL 32 (1) : 10-16
Comparative Efficacy of Nebulized L-adrenaline versus Salbutamolin Infants with Acute BronchiolitisAbstractBackground: Bronchiolitis is one of the most prevalent diseases of infancy for whichlarge number of infants need hospitalization, particularly during winter period. RSV(Respiratory syncitial virus) is the principal causative pathogenic organism. Relivingsymptoms are the main aim of management though none of the treatment modalitiesis specific. Bronchodilators like salbutamol, adrenaline, anti-cholinergic drugs,ipratropium bromide and saline nebulization have been used with varying results.Methods: This prospective study included 52 infants (2-12 months, male:female ratio 2:1)with bronchiolitis (with 1st episode of wheeze, previously healthy baby, physical findingswith cough, running nose, fever, coryza and inflation of lungs) to understand comparativeefficacy of nebulized salbutamol with adrenaline in bronchiolitis. The cases wererandomized into nebulized salbutamol group (n=25) and nebulized adrenaline group (n=27).After randomization three nebulization were given at the interval of 20 minutes. Outcomeof therapy was evaluated by respiratory rate, MRDAI (Modified Respiratory DistressAssessment Instrument) score and O saturation before and after therapy.Results: Study cases in both the groups presented with cough (100%), respiratorydistress (100%), feeding difficulty (90.3%), running nose (98%) and wheeze (100%).Majority of the cases live in urban area and mostly from non-smoker family. Insalbutamol group respiratory rate, MRDAI score and O saturation (before nebulizationRR-67.5±6.1, MRDAI score-14.6±1.3, SaO 93.9±1.6 and after nebulization RR-52.5±4.9, MRDAI score-6.4±1.7, SaO -97.1±1.5) significantly improved after 3nebulizations. In adrenaline group respiratory rate, MRDAI score and O saturation(before nebulization RR-64.9±5.9, MRDAI score-15.0±0.8, SaO 94.1±1.4 and afternebulization RR-50.0±2.9, MRDAI score-7.7±1.0, SaO -97.9±1.5) also significantlyimproved after 3 nebulizations. Improvement was more significant in adrenaline group.Heart rate in both groups were increased (salbutmol group-151.8±10.6 and in adrenalinegroup-160.2±10.1) but more in adrenaline group. When comparative efficacy evaluated,it was observed that nebulized adrenaline therapy was significantly superior to nebulizedsalbutamol therapy in reliving symptoms (p=.004).Conclusion: The study concluded that both nebulized salbutamol and l-adrenalineare effective and nebulized l- adrenaline is significantly superior to nebulized salbutamolin infant with bronchiolitis in reliving symptom.Key words: Nebulized l-adrenaline, nebulized salbutamol, acute bronchiolitis.Introduction
virtually all children become infected during first 3 year
Bronchiolitis is an acute viral inflammatory lesion of
of life1. Bronchiolitis occurs most commonly in male
small airways. More than 70% cases are due to
infants who have not been breastfed and live in
respiratory syncytial virus (RSV), other pathogens are
crowded condition. The source of viral infection is
Parainfluenza virus, Adenovirus, Rhinovirus, Influenza
usually a family member with minor respiratory illness.
virus and Mycoplasma pneumonae. The occurrence
Infants whose mothers smoke cigarette are more likely
is highest in mid winter to late spring. The peak
to acquire bronchiolitis than infants of non-smoking
incidence of bronchiolitis is 2-6 months of age and
mother. The occurrence is more observed where a
1. OSD, Department of Paediatrics, BSMMU, Shahbag, Dhaka
heavy smoker stays with children2. In USA >90,000
2. Professor of Paediatric Pulmonology, BICH, Dhaka Shishu
hospital admissions yearly are due to bronchiolitis,
Correspondence: Dr. AKM Amirul Morshed
the majority of infants younger than 90 days3.
Comparative Efficacy of Nebulized L-adrenaline versus Salbutamol
BANGLADESH J CHILD HEALTH 2008; VOL 32 (1) : 11
Variation in the management of bronchiolitis has been
After selecting the cases relevant history and physical
documented. Hospitalized patients receive a variety of
examination finding were recorded in a pretested
treatment modalities with uncertain efficacy such as
questionnaire. Heart rate, respiratory rate and the
bronchodilator, ribavirin, steroids and antibiotics. These
severity of illness were assessed by using a
variant modalities of treatment significantly impact the
combination of MRDAI score (Modified Respiratory
cost and adverse events associated with hospitalization4.
Distress Assessment Instrument) (Table-1) and O2
saturation. Oxygen saturation was measured non-
Bronchodilators are often used in the treatment of
invasively using pulse oxymeter, and those with values
bronchiolitis but data on efficacy are conflicting. Most
less than 92% were designated as having significant
studies have shown no beneficial effect on lung
mechanics. JD Kellner et al done an evidence based studywhere they commented that bronchodilator produce
The cases were then randomly (one case to salbutamol
modest short term improvement in clinical scores5.
group and next case to adrenaline group) assignedinto two groups designated as A (salbutamol group)
In an article, Arivolli Verappan and Ashir Kumar
and B (adrenaline group). Group A (salbutamol group)
described that any form of steroid is effective inbronchiolitis, specially nebulized budesonide 1000
received salbutamol in a dose of 0.15 mg/kg body
micro-gram/dose. They also comment that L-
weight (minimum dose 1 mg)7 diluted in normal saline
epinephrine was effective as well as less costly in
to make a total volume of 3 ml. Cases in group B
treatment of bronchiolitis6. Ribavirine a broad
(adrenaline group) received nebulization with 0.1 ml/
spectrum anti viral agent is the only specific therapy
kg body weight of 1 in 10,000 solution of adrenaline (1
for RSV infection in infant1. Ray and Singh concluded
ampoule 1:1000 injection diluted with 9 ml of normal
in a recent study that both nebulized epinephrine and
saline to make it 1 in 10000 solution) 7. The drug was
salbutamol caused significant improvement in mean
further mixed with normal saline to make a total volume
symptom score and oxygenation. However the
of 3 ml. Nebulization in each groups were given at 20
epinephrine group showed a significantly better
minutes intervals. Pulse oxymetry (NBP-40, Nellcor-
improvement in study parameters than salbutamol
Puritan Benett, Ireland) was done during this period
group. They concluded by saying “Adrenaline is more
and SaO values were recorded before and after
effective than salbutamol and is thus a better,
nebulization. No other drugs like antibiotics, steroids,
inexpensive and relatively safe alternative”7.
intravenous fluids, etc were given during this period.
Bertrand P et al had been done a prospective study on
In febrile cases only hydrotherapy was given.
efficacy of nebulized epinephrine versus salbutamol in
Ten minutes after administration of the last dose,
hospitalized infants with bronchiolitis. They commented
respiratory rate, MRDAI score and oxygen saturation
that nebulized epinephrine decreased the baseline
(by pulse oxymetry) were evaluated again to assess
clinical score of bronchiolitis faster than salbutamol.
the response to therapy. The decision for further
They also concluded that nebulized epinephrine is more
management was taken on the basis of this evaluation.
effective agent than salbutamol in the initial treatment
Children who showed a sustained decrease in
of bronchiolitis and is equally safe8.
tachypnea and respiratory distress (wheezing and
The study was conducted to understand the
retractions), and were accepting well orally after an
comperative efficacy of nebulized salbutamol versus
observation period of 1 hour, were sent home with oral
nebulized l-adrenaline in reliving in acute bronchiolitis.
medication. Children who did not improve admitted inhospital for further management.Materials and MethodsThe study was a prospective, randomized,
Supportive measures like propped up positioning, fluid,
interventional study conducted at Dhaka Shishu
feeding and antibiotics (whenever indicated) and
(Children) Hospital from July 2002 to December 2003.
counseling was done. MRDAI score was chosen to
Previously healthy infants (2-12 months) having first
assess the clinical outcome of nebulized salbutamol
episode of wheeze accompanying physical findings
and adrenaline because it is clinically relevant and
of viral infection i.e., coryza, cough, fever, etc and
has undergone validation and reliability measurement
evidence of hyperinflation of the lungs clinically and
in randomized controlled trials involving patients with
radiologically were included in this study. The patients
with evidence of similar previous attack, asthma,previous use of corticosteroid and history of atopy or
Data was analyzed by using SPSS statistical software
allergy and presence of congenital heart disease and
employing appropriate statistical tests like paired and
BANGLADESH J CHILD HEALTH 2008; VOL 32 (1) : 12
Respiratory distress assessment instrument9
Twenty cases (20/25; 80%) in salbutamol group and
The study included 52 cases, 25 (male-15, female-
23 cases (23/27; 85%) in adrenaline group live in urban
09) in nebulized salbutamol group, 27 (male-17,
area and 05 cases (5/25; 20%) in salbutamol group
female-10) in nebulized adrenaline group. Most of the
and 4 cases (4/27; 15%) live in rural area. Majority of
cases (salbutamol group-25, adrenaline group-24) in
the cases (salbutamol group-19/25; 76% and
both the groups were born at term and 42 (salbutamol
adrenaline group-23/27; 85%) live in normal
group-21, adrenaline group-21) infants were delivered
environment. Minority of the cases (salbutamol group-
normally. Body weight of the cases ranged from 4.5
6/25; 24% and adrenaline group-4/27; 15%) lives in
crowded environment. Majority of the cases(salbutamol group-21/25; 84% and adrenaline group-
Majority in salbutamol (17/25; 68%) and adrenaline
24/27; 89%) lives in well-ventilated rooms. Ventilation
group (17/27; 63%) were exclusively breastfed up to
of the rest of the families was poor. In salbutamol
4 months of age. Only 2 cases in both groups had
group 12 (11/25; 44%) family members were smokers
combined breast feeding and complementary feeding.
while it was 6 (6/27; 22.2%) in adrenaline group.
Only complementary feeding was given to 6 cases
Majority of the family members 34(13/25; 52% in
(6/25; 24%) in salbutamol group versus 8 cases (8/
salbutamol group and 21/27; 77.8% in adrenaline
Table-IIResidence of the family, crowded living and ventilation status distribution
Comparative Efficacy of Nebulized L-adrenaline versus Salbutamol
BANGLADESH J CHILD HEALTH 2008; VOL 32 (1) : 13
Table-III
(97.1±1.5) and RDAI score (6.4±1.7) had
significantly improved in comparison to respiratory
rate (67.5±6.1), oxygen saturation (93.9±1.6) and
RDAI score (14.6±1.3) of before nebulization
(p=<.001 in all parameter). Heart rate also
significantly increased after nebulization (151.8±10.6
After nebulized adrenaline therapy mean respiratory
rate (50.0±2.9), oxygen saturation (97.9±0.8), RDAI
score (7.7±0.1) had also significantly improved in
comparison to respiratory rate (64.9±5.9), oxygen
saturation (94.11±2.9) and RDAI score (15.04±0.8)
All the cases presented with cough but 98% of the
before nebulization (p=<.001 in all parameter). Mean
cases presented with running nose (salbutamol group-
heart rate was significantly increased after
24/25; 96% and adrenaline group-27/27; 100%).
nebulization (160 ±10.1 versus 105, ±10.04)
Difficulty of feeding was a presenting feature in 21
(84%) patients of salbutamol group and 26 (96%)
patients in adrenaline group. Only in 16 cases in both
In comparison between two modalities of treatment,
groups (salbutamol group-16/25; 64% and adrenaline
adrenaline was found to be significantly more
group-16/27; 59%) presented with fever (98ºF -103ºF).
efficacious than salbutamol in every parameter except
All the cases were presented with wheeze and
in MRDAI score after nebulization where p value was
0.08. But in respiratory rate (p=.03), oxygen saturation
On examination of the lungs, 33 (63.5%) patients had
(p=.03) and MRDAI score reduction (.004) was
no significant auscultatory finding and spleen was
significantly better in adrenaline group after 3rd
palpable in 10 (19.2%) patients. Asthma, eczema and
allergic rhinitis (atopic conditions) were present in only
We have done RSV antigen of nasal swab in 25 (48%)
patients of both groups and found only 4(16.0%)
patients were positive for RSV antigen. Here group
respiratory rate (52.5±4.9), oxygen saturation
Table-IVComparison of response to therapy with nebulized salbutamol versus adrenaline
BANGLADESH J CHILD HEALTH 2008; VOL 32 (1) : 14
Discussion
60% of cases had RSV positive antigen in their nasal
The present study included 52 cases, 25 (male-15,
female-09) in nebulized salbutamol group, 27 (male-
Comparing nebulized salbutamol with adrenaline there
17, female-10) in nebulized adrenaline group. Male
was significant improvement of respiratory rate and
infants are predominantly affected with bronchiolitis
O saturation and difference of improvement between
in both the groups7,10. Most of the cases in both the
the two groups after 3rd nebulization was statistically
groups were born at term and delivered normally. Body
significant. One study in neighbouring country also
weight of the cases ranged from 4.5 kg to 13 kg (mean-
observed significant improvement by nebulized
6.5 kg). In an Indian study mean age was 5.6 months7.
salbutamol and adrenaline therapy and the efficacy of
Majority cases in both salbutamol and adrenaline
nebulized adrenaline was significantly superior to
groups were exclusively breast-fed up to 4 months.
salbutamol7. Menon et al observed no significant
Only 2 cases in both the groups had mixed feeding.
difference between nebulized salbutamol and
Only complementary feeding was given to 6 cases in
salbutamol group versus 8 cases in adrenaline group.Though breast feeding has a protective effect against
In the present study (Table-IV) mean O saturation
infection the present study showed that breast fed
before nebulization were 93.9% and 94.1% in
babies also suffer with bronchiolitis. Twenty cases
salbutamol and adrenaline group respectively. After
(80%) in salbutamol group and 23 cases (85.2%) in
nebulization mean oxygen saturation raised upto
adrenaline group live in urban area and few cases live
97.1% and 97.8% in salbutamol and adrenaline group
in rural area. Here urban infants are affected more
respectively, which is statistically significant. In
and it is established inference for bronchiolitis2.
another Indian study SaO before nebulization was
Majority of the cases live in normal environment and
91.1% and 90.6% in salbutamol and adrenaline group
in well-ventilated rooms. Though living in well-ventilated
respectively and after nebulization these score raised
room, majority of the cases had attack of bronchiolitis.
to 93.9% and 98.0% respectively7, similar to our study.
Forty-seven mothers are housewives and only 4
In a canadian study there was no significant
mothers work outside home. In salbutamol group only
improvement in O saturation when compared with
12 family members were smokers versus 6 in
before and after nebulization salbutamol versus
adrenaline group. Majority of the family members of
adrenaline14. Ainiune AA et al compared the efficacy
both the groups were non-smokers. Though smoking
of nebulized adrenaline with nebulized normal saline
is a recognized risk factor for bronchiolitis, particularly
and concluded that adrenaline is not superior to normal
saline13. An earlier trial on croupy infants had revealedthat the peak effect of nebulized epinephrine appeared
In the present study running nose, cough, wheeze,
in 30 minutes and lasted for 60-90 minutes15. In this
fever and feeding difficulty were predominant presenting
study even though the continued effect of the drugs
features in both the groups (Table-III). All the cases
was seen after the third dose, the maximal change in
(100%) of the present study presented with cough
SaO appeared in both groups after the second
and 94% cases presented with running nose. Difficulty
of feeding was a presenting feature in 75% cases in
nebulization, i.e., about 30 minutes after the onset of
salbutamol group and almost all cases in adrenaline
nebulization. This may perhaps explain why certain
group. Only 16 cases in both the groups presented
authors who used only a single dose of adrenaline
with fever (up to 1030F). One study in Bangladesh
failed to observe any significant improvement16.
observed that clinical presentations were almost similar
MRDAI (Respiratory Distress Assessment Instrument)
to our study10. L kabir et al found that spleen was
score reduction in our study was 6.1 and 7.3 in
palpable in 42% cases while it was only 19% in present
salbutamol and adrenaline group respectively, which
is statistically significant. Reduction of MRDAI score
We tested only 25 samples of nasal swabs out of
in adrenaline group is significantly better than
total 52 cases for RSV where only nasal swabs of 4
salbutamol group in our study which was also shown
patients had RSV antigen positive. A previous study
by a previous Indian study where mean score reduction
in Bangladesh showed 45.0% anti RSV antibody (IgM)
was 8.8 and 5.9 in adrenaline and salbutamol groups
positive cases10. A study in England reported that
respectively7. A study in Canada, MRDAI score
Comparative Efficacy of Nebulized L-adrenaline versus Salbutamol
BANGLADESH J CHILD HEALTH 2008; VOL 32 (1) : 15
reduction was 7.5 and 6.6 in salbutamol and adrenaline
be safely used in reliving of symptoms in bronchiolitis
groups respectively, which did not have any statistical
without any major side effects. Larger, multicentre,
significance14. Ainine AA has also shown no significant
double blind, randomized controlled trials are required
difference regarding RDAI score reduction between
adrenaline and saline nebulization13.References
In our study, we have used a combination of MRDAI
score and oxygen saturation to assess the respiratory
Advances in Treatment. Indian J Pediatr 1996;
functional status and degree of distress. These score
are non-invasive, have low inter-observer variation and
Orenstein DM. Bronchiolitis. In: Behrman RE,
can be easily evaluated in the OPD set-up. Arterial
oxygen saturation by pulse oxymetry has suggestedbeing the best objective criterion to assess degree of
Textbook of Pediatrics. 17th ed. Philadelphia: WB
Analysis of the present study also revealed that the
children in both the groups had similar clinical profile
Byington CL. Sepsis evaluation in hospitalizedinfants with bronchiolitis. Pediatr Infect Dis J
during the time of inclusion in the study. After
nebulization for three times consecutively, within 20minutes interval both the adrenaline and salbutamol
Klassen TP, Rowe CP, Sutclife T, Roop LJ,
groups showed significantly improvement which was
more marked in the adrenaline group in comparison
salbutamol in acute bronchiolitis. J Pediatr 1991;
to salbutamol group in all parameters. Not only the
mean score and mean SaO levels were better in the
adrenaline group but also more proportion of patients
EEL. Bronchodilator therapy in Bronchiolitis.
significantly improved both in clinical scores as well
as oxygen saturation in adrenaline group comparedto salbutamol group (p< 0.03).
Verappan A, Kumar A. Role of steroid in croupand beta agonist in Bronchiolitis. Indian Pediatr
The cardiac side effects of drugs used were also
assessed because the chronotropic action ofadrenegric agents on the heart is often a matter of
concern. Both salbutamol as well as adrenaline
showed a significant increase in heart rate that was
associated respiratory tract infection in infants.
more in case of adrenaline group. However, this study
did not have any adverse clinical effects like increased
Bertrand P, Aranibar H, Castro E, Sanchez I.
irritability, tremors, facial blanching, arrhythmia,
congestive heart failure and none of the children
required drug withdrawal or intervention for tachycardia
Bronchiolitis. Pediatr Pulmon 2001; 31: 28.
Lowell DI, Lister G, Von Koss H, MacCarthy P.
Bronchodilator, both specific (β agonist e.g,
salbutamol) and nonspecific agonist (adrenaline) are
epinephrine. Pediatrics 1978; 79: 939-45.
useful in relieving symptoms and improving
10. Kabir ARML, Haq N, Hoque M, Ahmed F, Amin
R, Hossain A, et al. Evaluation of hospital infantsand young children with Bronchiolitis - a
Conclusion
multicentre study. Mymensingh Medical Journal
The study concluded that both salbutamol and l-
adrenaline are useful in relieving symptoms andimproving oxygenation in bronchiolitis. When
Mc Connochie, Roghman KJ. Parental Smoking,
comparative efficacy was evaluated it was observed
presence of older siblings and familly history of
that nebulized l-adrenaline was superior to nebulized
asthma increase risk of asthma. Am J Dis Child
salbutamol in bronchiolitis. Nebulized adrenaline can
BANGLADESH J CHILD HEALTH 2008; VOL 32 (1) : 16
12. Mc Connochie, Roghman KJ. Bronchiolitis as a
randomized double blind study comparing L-
possible cause of wheezing in childhood. New
epinephrine and racemic epinephrine aerosols
evidence. Pediatrics 1984; 74: 1-10.
in the treatment of laryngotracheitis (croup).Pediatrics 1992; 89: 302-06.
13. Ainiune AA, D Leyf. Short term effect of
Adrenaline in Bronchiolitis: a randomized
16. Lenney W, Milner AD. Alpha and beta adrenergic
controlled trial. Arch Dis Child 2002; 86: 276-79.
stimulants in bronchiolitis and wheezy bronchitisin children under eighteen months of age. Arch
14. Menon K, Sutcliff T, Klassen TP. A randomized
trial comparing the efficacy of epinephrine withsalbutamol in the treatment of acute bronchiolitis.
17. Henerson FE, Clyde WA, Collier AM, Denny FW,
Senior RJ, Sheaffer CT, et al. The etiology andepidemiologic spectrum of bronchiolitis in
15. Waisman Y, Klein BL, Boenning DA, Young GM,
pediatric practice. J Pediatr 1979; 86: 95-100.
Chamkerlain JM, O’Donnel R, et al. Prospective

Reporter's Notebook: German Drug Firm Provides Cipro Ever since Tom Brokaw ended a newscast with the words, "In Cipro we trust," this brand of antibiotic has been on every American's lips. And so has "Bayer," the German company that makes the drug. Bayer (pronounced in German like the English word "buyer") has been a household name since the early 1900s when the f

We define sports therapy as the enjoyment of any sport whichresults in improvements in gross motor function for individ-uals having neurological disorders or developmental disabil-ities. The introduction of sports therapy in the early formativeyears may have a significant impact on accelerating the reha-bilitation of children with neurological disorders or develop-mental disabilities, such as ce